Several disorders arising from hyposecretion of one or more substances such as hormones are known. Among these are diabetes, Parkinson's disease, Alzheimer's disease, hypo- and hyper-tension, hypothyroidism, and various liver disorders. The hormone insulin, for example, is produced by β-cells in the islets of Langerhans of the pancreas. In normal individuals, insulin release is regulated so as to maintain blood glucose levels in the range of about 70 to 110 milligrams per deciliter. In diabetics, insulin is either not produced at all (Type 1 diabetes), or the body cells do not properly respond to the insulin that is produced (Type 2 diabetes). The result is elevated glucose levels in the blood.
Disorders arising from hyposecretion of a hormone are usually treated by administration of the missing hormone. However, despite advances in understanding and treating many of these diseases, it is often not possible to precisely regulate metabolism with exogenous hormones. A diabetic patient, for example, is required to make several daily measurements of blood glucose levels and then inject an appropriate amount of insulin to bring the glucose levels to within the acceptable range.
Organ transplantation is not a viable treatment today for most of these disorders for several reasons including rejection of a transplanted organ by the immune system. Isolated cells may be implanted in the body after being treated to prevent rejection e.g. by immunosuppression, radiation or encapsulation. The encapsulating material is selected so as to be biocompatible and to allow diffusion of small molecules between the cells and the environment while shielding the cells from immunoglobulins and cells of the immune system. Encapsulated β-cells or islets of Langerhans (the tissue producing the insulin), for example, can be injected into the portal vein or embedded under the skin, in the abdominal cavity, or in other locations. The success of many cellular transplants is compromised not only due to graft-host rejections, but also on account of ischemic conditions generated by insufficient oxygen supply to the transplant. Following implantation of the cells, oxygen is provided to the implanted cells from the body tissue (mainly via diffusion), and in some cases, from vascular structures that form around the transplanted cells with the help of angiogenic factors, e.g., VEGF and bFGF. However, the natural diffusion rate is too low to provide the cells with a sufficient amount of oxygen, especially in macro-encapsulation and high density of the cells.
Oxygen is vital for the physiological processes and functionality of the implanted cells. An insufficient supply of oxygen to the implanted cells, often leads to cell loss of functionality or death. Oxygen provision is a vital component in sustaining transplanted cells.
Attempts are made to assure sufficient oxygen to the implanted cells. U.S. Pat. No. 7,892,222 entitled “Implantable Device”; to Vardi et al., teaches an implantable device comprising a chamber for holding functional cells and an oxygen generator for providing oxygen to the functional cells.
In one embodiment, the oxygen generator is described as comprising photosynthetic cells that convert carbon dioxide to oxygen when illuminated. In another embodiment, the oxygen generator is described as comprising electrodes that produce oxygen by electrolysis.
U.S. Pat. No. 8,012,500 to Rotem et al. describes apparatus including a chamber, which is adapted to be implanted in a body of an individual, the chamber including functional cells and chlorophyll-containing elements comprising chlorophyll of an obligate photoautotroph. Typically, the chlorophyll-containing elements include intact photosynthetic cells and/or isolated chloroplasts. The chlorophyll-containing elements provide oxygen to the functional cells and/or consume carbon dioxide produced by the functional cells.
U.S. Pat. No. 8,444,630 titled “Oxygen Supply for Cell Transplant and Vascularization” to Rotem, et al. describes an apparatus including a housing configured for insertion into a body of a patient; a photosynthetic oxygen supply configured to supply oxygen; and functional cells, coupled to the housing. The functional cells are adapted to receive the oxygen and to secrete at least one factor that induces vascularization in a vicinity of the housing when the housing is in the body of the patient. Other embodiments are also described.
When no oxygen reservoir is present, configurations of the implants is desired. An example is taught in U.S. Pat. No. 5,855,613 to Antanavich et al., entitles Retrievable Bioartificial Implants having Dimensions Allowing Rapid Diffusion of Oxygen and Rapid Biological Response to Physiological Change. This patent describes bioartificial implants and methods for their manufacture and use, particularly bioartificial pancreases. In particular, the implants may be thin sheets that enclose cells or tissue, may be completely biocompatible over extended periods of time and may induce minimal fibrosis. The viability of the high-density-cell-containing thin sheets is achieved by nourishing the tissue or cells with sufficient oxygen supply. The device is completely retrievable, and have dimensions allowing maintenance of optimal tissue viability through rapid diffusion of nutrients and oxygen and also allowing rapid secretion rate of insulin and/or other bioactive agents in response to changing physiology. Implantations of living cells, tissue, drugs, medicines and/or enzymes, contained in the bioartificial implants may be made to treat and/or prevent diseases.